The lymphoid cells known as natural killer (NK) cells are thought to provide the first line of defense against developing neoplasms. It has been previously shown that upon mixing populations of NK cells with appropriate target cells, the NK cells first bind and then lyse the target cells. However, the mechanisms involved in the recognition and ultimate lysis of the target cell are unknown. The recent development of research techniques which follow very rapid electrical events in the membranes of single cells may provide an opportunity of studying this interaction with much greater detail and resolution. The specific aims of this project will be to: (1) develop new techniques for single cell manipulation to facilitate the study of NK-target cell interaction, (2) apply the patch-clamp recording technology to measure changes in membrane potential, resistance and capacitance in either the NK or the target cell during the process of cell contact and lysis, and (3) develop a modified version of the patch-clamp that will preferentially record electrical events and membrane capacitance in the area of cell-cell contact. If these studies show a correlation between immune cell function and electrical activity, this technology will provide the first precise observations of the events that lead from cell-cell contact to target cell lysis. It is anticipated that the techniques developed in this study will prove useful in further investigations of these and other immune cell functions.